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Elevated Plasma Vitamin B12 Levels Associated With Cancer Risk

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Key Points

  • Elevated cobalamin levels were associated with significantly increased risk of all cancers, with risk being greatest during the first year of follow-up.
  • Significantly increased risk was observed for smoking- and alcohol-related cancers and hematologic cancers, with higher cobalamin levels being associated with a persistent increase in risk.

High plasma levels of vitamin B12 (cobalamin) have been reported in patients with cancer of different types. In a Danish study reported in the Journal of the National Cancer Institute, Arendt et al assessed cancer risk in subjects presenting with elevated cobalamin. They found that cancer risk increased with increasing cobalamin level and was greatest in the first year of follow-up.

Study Details

In this cohort study, subjects referred for cobalamin measurement who had levels greater than the lower reference limit (200 pmol/L) were identified from the population of Northern Denmark during the period of 1998 to 2009, using a database of laboratory test results covering the entire population. Data on cancer incidence during follow-up from 1998 to 2010 and prior diagnoses were obtained from medical registries. Patients receiving cobalamin treatment were excluded from the analysis.

Of 333,667 persons without prevalent cancer, 19,665 (6%) had cobalamin levels greater than the upper reference limit of 600 pmol/L. The total number of person-years of follow-up was 1,421,512, and median follow-up was 3.5 years. Median age of subjects was 55 years. A total of 22,652 subjects (7%) developed cancer between 1998 and 2010.

Overall, cancer was diagnosed in 6.7% of subjects with cobalamin levels of 200 to 600 pmol/L, 7.8% of those with levels 601 to 800 pmol/L, and 11.0% of those with levels > 800 pmol/L, with cancer occurring in 2.3%, 3.7%, and 6.6% during the first year of follow-up, and in 4.4%, 4.1%, and 4.4% thereafter.

Increased Risk Highest in First Year

The overall standardized incidence ratio (SIR, ie, the ratio of observed cancers to expected cancers) for all cancers was 1.61 (95% confidence interval [CI] = 3.14–3.76) in subjects with cobalamin levels of 601 to 800 pmol/L and 2.38 (95% CI = 2.22–2.56) in those with levels > 800 pmol/L.

Risk increased with increasing cobalamin level and was greater in the first year of follow-up (SIRs of 3.44 and 6.27 for levels 601–800 and > 800 pmol/L; P < .001 for both) than at > 1 year (SIRs of 1.09 and 1.24). The risk increase with increasing cobalamin level was greater in subjects aged < 50 years than in older subjects, and risk was greater for men (SIRs of 1.93 and 2.94 for levels of 601–800 and > 800 pmol/L) than women (SIRs of 1.43 and 2.05)

Standardized incidence ratios for the 601 to 800 and > 800 pmol/L categories were 2.13 and 3.05 for smoking- and alcohol-related cancers (first-year SIRs of 4.89 and 8.37, respectively), 2.27 and 7.96 for hematologic cancers (first-year SIRs of 6.82 and 24.14), 1.17 and 0.97 for immune-related cancers (first-year SIRs of 1.89 and 1.37), and 1.12 and 1.19 for hormone-related cancers (first-year SIRs of 1.96 and 2.61).

After the first year, risk remained elevated in the 601 to 800 pmol/L category for smoking- and alcohol-related cancers (SIR = 1.33) and in the > 800 pmol/L category for smoking- and alcohol-related cancers (SIR = 1.44) and hematologic cancers (SIR = 2.99). Standardized incidence ratios remained elevated for smoking- and alcohol-related cancers and hematologic cancers (only in the > 800 pmol/L category) at > 5 years of follow-up.

The investigators concluded, “High [cobalamin] levels were associated with the risk of subsequently diagnosed cancer, mostly within the first year of follow-up. This may have clinical implications for the interpretation of high [cobalamin] levels.”

Johan Frederik Berg Arendt, BSc, of Aarhus University Hospital, is the corresponding author for the Journal of the National Cancer Institute article.

The study was supported by Aarhus University; Aarhus University Hospital; Frits, Georg, and Marie Cecilie Gluds Foundation; Else og Mogens Wedell-Wedellborgs Foundation; The Danish Cancer Society; and Karen Elise Jensen Foundation.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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